Down-regulation of ARID1A is sufficient to initiate neoplastic transformation along with epigenetic reprogramming in non-tumorigenic endometriotic cells.

ABSTRACT: The chromatin remodeler AT-Rich Interactive Domain 1A (ARID1A) is frequently mutated in ovarian clear cell carcinoma (OCCC) and endometriosis precursor lesions. Here, we show that knocking down ARID1A in an immortalized endometriosis cell line is sufficient to induce phenotypic changes indicative of neoplastic transformation as evidenced by higher efficiency of anchorage-independent growth, increased propensity to adhere to collagen, and greater capacity to invade basement membrane extract in vitro. ARID1A knockdown is associated with expression dysregulation of 99 target genes, and many of these expression changes are also observed in primary OCCC tissues. Further, pathway analysis indicates these genes fall within networks highly relevant to tumorigenesis including integrin and paxillin

SUBMITTER: Lakshminarasimhan R 

PROVIDER: S-EPMC5645058 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature